In order to study the ionization mechanism in MALDESI, the RASTIR source was implemented to separate in space the laser desorption event from the intersecting electrospray ionization beam. Deuterated solvents were electrosprayed from the RASTIR source which resulted in a near complete shift from [M + H(+)](1+) to [M + D(+)](1+) of the monoisotopic peak for reserpine. The purpose of these experiments is to test the hypothesis that the primary ionization pathway in MALDESI is through interaction of the laser-desorbed neutral species with the intersecting electrospray ionization beam. The combination of RASTIR coupled to MALDESI can be utilized to study small organic molecules as well as peptides and proteins. Moreover, the use of RASTIR combined with MALDESI lends itself to improve the overall efficiency of ionization.

A commercial air ejector was coupled to an electrospray ionization linear ion trap mass spectrometer (LTQ) to transport remotely generated ions from both electrospray (ESI) and desorption electrospray ionization (DESI) sources. We demonstrate the remote analysis of a series of analyte ions that range from small molecules and polymers to polypeptides using the AE-LTQ interface. The details of the ESI-AE-LTQ and DESI-AE-LTQ experimental configurations are described and preliminary mass spectrometric data are presented. (J Am Soc Mass

The use of aerodynamic devices in ambient ionization source development has become increasingly prevalent in the field of mass spectrometry. In this study, an air ejector has been constructed from inexpensive, commercially available components to incorporate an electrospray ionization emitter within the exhaust jet of the device. This novel aerodynamic device, herein termed remote analyte sampling, transport, and ionization relay (RASTIR) was used to remotely sample neutral species in the ambient and entrain them into an electrospray plume where they were subsequently ionized and detected using a linear ion trap Fourier transform mass spectrometer. Two sets of experiments were performed in the ambient environment to demonstrate the device's utility. The first involved the remote (approximately 1 ft) vacuum collection of pure sample particulates (i.e., dry powder) from a glass slide, entrainment and ionization at the ESI emitter, and mass spectrometric detection. The second experiment involved the capture (vacuum collection) of matrix-assisted laser desorbed proteins followed by entrainment in the ESI emitter plume, multiple charging, and mass spectrometric detection. This approach is in principle a RASTIR-assisted matrix-assisted laser desorption electrospray ionization source (Sampson, J. S.; Hawkridge, A. M.; Muddiman, D. C. J. Am. Soc. Mass Spectrom. 2006, 17, 1712-1716; Rapid Commun. Mass Spectrom. 2007, 21, 1150-1154.). A detailed description of the device construction, operational parameters, and preliminary small molecule and protein data are presented.

An initial investigation into the effects of charge separation in the Array of Micromachined UltraSonic Electrospray (AMUSE) ion source is reported to gain understanding of ionization mechanisms and to improve analyte ionization efficiency and operation stability. In RF-only mode, AMUSE ejects, on average, an equal number of slightly positive and slightly negative charged droplets due to random charge fluctuations, providing inefficient analyte ionization. Charge separation at the nozzle orifice is achieved by the application of an external electric field. By bringing the counter electrode close to the nozzle array, strong electric fields can be applied at relatively low DC potentials. It has been demonstrated, through a number of electrode/electrical potential configurations, that increasing charge separation leads to improvement in signal abundance, signal-to-noise ratio, and signal stability. (J Am Soc Mass

The design and implementation of a radio frequency acoustic desorption ionization (RADIO) source has been demonstrated for the analysis of multiply charged peptides and proteins. One L aliquots of melittin, BNP-32, and ubiquitin ( ϳ1 g of analyte) were deposited onto a quartz crystal microbalance (QCM) electrode before radio frequency actuation for desorption. Continuous electrospray parallel to/above the sampling surface enabled the ionization of Laser-induced acoustic desorption (LIAD) [1-4] demonstrates the soft desorption of analyte using a shock wave generated by a laser pulse and the potential to couple post-desorption ionization techniques such as chemical ionization at atmospheric pressure. Array of micro-machined ultrasonic electrosprays [5][6][7] (AMUSE), applies an rf signal to a ceramic piezoelectric transducer with a solution cavity between a micromachined silicone nozzle array for droplet-on-demand generation. The preceding techniques address RADIO's desorption mechanism. Several other techniques are mentioned below as they utilize postdesorption ionization (as in RADIO). Secondary electrospray ionization (SESI) [8 -11] involves the gas-phase interaction of charged ESI droplets with neutral sample molecules for analysis by ion mobility spectrometry (IMS) or MS. Fused droplet electrospray ionization (FD-ESI) [12,13] aerosolizes the sample solution via a nebulizer for interaction with a highly charged acidic methanol solution and reduces interferences from buffers and complex mixtures. Extractive electrospray ionization (EESI) [14 -18] employs two nebulizing sprayers, one with ESI solvents and a second containing the analyte of interest for a liquidliquid extraction process to reduce interferences from complex mixtures.Closely related to RADIO due to step-wise desorption with subsequent ionization are electrosprayassisted laser desorption ionization (ELDI) [19] and solid-state matrix assisted laser desorption electrospray ionization (ss-MALDESI) [20,21]. ss-MALDESI utilizes a UV or IR laser for analyte desorption and ESI for post-ionization.The desorption phenomena can be attributed in part to the shock wave desorption observed in LIAD, however for RADIO, the transfer of energy is accomplished by applying an rf waveform to a piezoelectric material (analogous to AMUSE). Postdesorption electrospray is the proposed ionization pathway as in SESI, FD-ESI, EESI, and ss-MALDESI. Experimental MaterialsMelittin, BNP-32, ubiquitin, and formic acid were obtained from Sigma Aldrich (St. Louis, MO). HPLC grade acetonitrile and water were purchased from Burdick and Jackson (Muskegon, MI). Nitrogen (99.98%) and LTQ helium bath gas (99.999%) were obtained from MWSC High Purity Gases (Raleigh, NC). MethodsElectrospray solutions consisted of acetonitrile:water (50:50% by volume) with 0.1% formic acid. Melittin was diluted to 347 M in water, BNP-32 was diluted to 300 M in water with 0.1% formic acid, and ubiquitin was diluted to 99 M in 50:50:0.1% water:acetonitrile:formic acid. QCM substrates were spotted with 1 L of...